Voxel-Wise Map of Intracerebral Hemorrhage Locations Associated With Worse Outcomes.

Background: Prior studies on the clinical impact of intracerebral hemorrhage (ICH) location have used visual localization of hematomas to neuroanatomical structures. However, hematomas often cross neuroanatomical structure boundaries with inter-reviewer variability in visual localization. To address these limitations, we applied voxel-wise analysis to identify brain regions where ICH presence is independently predictive of worse outcomes.

Methods: We included consecutive patients with acute spontaneous ICH from a comprehensive stroke center in a derivation cohort and validated the results in patients from the control arm of a multicenter clinical trial. Using general linear models, we created and publicly shared a voxel-wise map of brain regions where ICH presence was associated with higher 3-month modified Rankin Scale scores, independent of hematoma volume and clinical risk factors. We also determined the optimal overlap threshold between baseline hematoma and voxel-wise map to categorize ICH location into high versus low risk.

Results: Excluding those with missing variables, head computed tomography processing pipeline failure and poor scan quality, 559 of 780 patients were included in derivation (mean age, 69.3±14.5 years; 311 [55.6%] males) and 345 of 500 (mean age, 62.5±12.9 years; 206 [59.7%] males) in validation cohorts. In a voxel-wise analysis, ICH presence in deep white matter, thalami, caudate, midbrain, and pons was associated with worse outcomes. At the patient level, >22% overlap of baseline hematoma with voxel-wise map optimally binarized ICH location to high- versus low-risk categories. In both the derivation and validation cohorts, a high-risk ICH location was independently associated with worse outcomes (higher 3-month modified Rankin Scale score), after adjusting for patients' age, symptom severity at admission, baseline hematoma volume, and the presence of intraventricular hemorrhage, with adjusted odds ratios of 2 ([95% CI, 1.3-3.0] P=0.001) and 1.7 ([95% CI, 1.1-2.9] P=0.027), respectively.

Conclusions: We created and publicly shared a voxel-wise map of brain regions where hematoma presence predicts worse outcomes, independent of volume and clinical risk factors.